Cologuard® colorectal cancer screening test is a registered trademark of Exact Sciences Corporation.
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`Cologuard® Physician Brochure
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`Indications for Use
`
`Cologuard is intended for the qualitative detection of colorectal neoplasia associated DNA markers and for the
`presence of occult hemoglobin in human stool. A positive result may indicate the presence of colorectal cancer
`(CRC) or advanced adenoma (AA) and should be followed by diagnostic colonoscopy. Cologuard is indicated
`to screen adults of either sex, 50 years or older, who are at typical average-risk for CRC. Cologuard is not a
`replacement for diagnostic colonoscopy or surveillance colonoscopy in high risk individuals.
`
`Contraindications
`
`Cologuard is intended for use with patients, age 50 years and older, at average risk who are typical candidates
`for CRC screening. Cologuard was not clinically evaluated for the following types of patients:
`
`o Patients with a history of colorectal cancer, adenomas, or other related cancers.
`o Patients who have had a positive result from another colorectal cancer screening method within
`the last 6 months.
`o Patients who have been diagnosed with a condition that is associated with high risk for
`colorectal cancer. These include but are not limited to:
`Inflammatory Bowel Disease (IBD)
`•
`Chronic ulcerative colitis (CUC)
`•
`Crohn’s disease
`•
`Familial adenomatous polyposis (FAP)
`•
`Family history of colorectal cancer
`•
`o Patients who have been diagnosed with a relevant familial (hereditary) cancer syndrome, such
`as Hereditary non-polyposis colorectal cancer syndrome (HNPCCC or Lynch Syndrome), Peutz-
`Jeghers Syndrome, MYH-Associated Polyposis (MAP), Gardner’s syndrome, Turcot’s (or
`Crail’s) syndrome, Cowden’s syndrome, Juvenile Polyposis, Cronkhite-Canada syndrome,
`Neurofibromatosis, or Familial Hyperplastic Polyposis.
`
`Warnings and Precautions
`
`(cid:120) The performance of Cologuard has been established in a cross sectional study (i.e., single point in
`time). Programmatic performance of Cologuard (i.e., benefits and risks with repeated testing over an
`established period of time) has not been studied. Performance has not been evaluated in adults who
`have been previously tested with Cologuard. Non-inferiority or superiority of Cologuard programmatic
`sensitivity as compared to other recommended screening methods for CRC and AA has not been
`established.
`(cid:120) CRC screening guideline recommendations vary for persons over the age of 75. The decision to screen
`persons over the age of 75 should be made on an individualized basis in consultation with a healthcare
`provider. Cologuard test results should be interpreted with caution in older patients as the rate of false
`positive results increases with age.
`(cid:120) A negative Cologuard test result does not guarantee absence of cancer or advanced adenoma.
`Patients with a negative Cologuard test result should be advised to continue participating in a colorectal
`cancer screening program with another recommended screening method. The screening interval for
`this follow-up has not been established.
`(cid:120) Cologuard may produce false negative or false positive results. A false positive result occurs when
`Cologuard produces a positive result, even though a colonoscopy will not find cancer or precancerous
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`polyps. A false negative result occurs when Cologuard does not detect a precancerous polyp or
`colorectal cancer even when a colonoscopy identifies the positive result.
`(cid:120) Patients should not provide a sample for Cologuard if they have diarrhea or if they have blood in their
`urine or stool (e.g., from bleeding hemorrhoids, bleeding cuts or wounds on their hands, rectal bleeding,
`or menstruation).
`(cid:120) To ensure the integrity of the sample, the laboratory must receive the patient specimens within 72
`hours of collection. Patients should send stool samples to the laboratory according to the instructions
`stated in the Cologuard Patient Guide.
`(cid:120) Patients should be advised of the caution listed in the Cologuard Patient Guide. Patients should NOT
`drink the preservative liquid.
`(cid:120) The risks related to using the Cologuard Collection Kit are low, with no serious adverse events reported
`among people in a clinical trial. Patients should be careful when opening and closing the lids to avoid
`the risk of hand strain.
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`RX Only
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`Table of Contents
`INDICATIONS FOR USE ................................................................................................................................................................................. 1
`CONTRAINDICATIONS .................................................................................................................................................................................. 1
`WARNINGS AND PRECAUTIONS ..................................................................................................................................................................... 1
`Table of Contents .................................................................................................................................................................... 2
`Cologuard Overview ................................................................................................................................................................ 3
`PATIENT SAMPLES FOR COLOGUARD .............................................................................................................................................................. 3
`COLOGUARD COMPLIANCE PROGRAM ............................................................................................................................................................ 3
`Colorectal Cancer Overview .................................................................................................................................................... 3
`Device Description .................................................................................................................................................................. 4
`ASSAY TECHNOLOGY ................................................................................................................................................................................... 4
`Clinical Study: Multi-Target Colorectal Cancer Screening Test for the Detection of Colorectal Advanced Adenomatous
`Polyps and Cancer (DeeP-C) .................................................................................................................................................... 4
`OVERVIEW ................................................................................................................................................................................................ 4
`STUDY DESIGN ........................................................................................................................................................................................... 5
`STUDY POPULATION AND BASELINE DEMOGRAPHICS ......................................................................................................................................... 5
`CLINICAL PERFORMANCE MEASURES .............................................................................................................................................................. 6
`SUMMARY OF CLINICAL STUDY RESULTS .......................................................................................................................................................... 6
`COLOGUARD AND FIT PERFORMANCE COMPARISON ......................................................................................................................................... 7
`COLOGUARD SUBGROUP ANALYSIS: PLEASE NOTE THAT THE CLINICAL STUDY WAS NOT DESIGNED TO EVALUATE SUBGROUPS AND SUBGROUP ANALYSIS
`SHOULD BE INTERPRETED WITH THAT IN MIND. ................................................................................................................................................. 8
`Ordering Cologuard ............................................................................................................................................................... 10
`SAMPLE COLLECTION ................................................................................................................................................................................. 10
`INTERFERING SUBSTANCES.......................................................................................................................................................................... 10
`INSTRUCTIONS FOR SAMPLE COLLECTION ...................................................................................................................................................... 10
`INTERPRETATION OF COLOGUARD ASSAY RESULTS .......................................................................................................................................... 11
`References ............................................................................................................................................................................ 12
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`Cologuard Overview
`Cologuard uses advanced multiple-marker, stool DNA technology to detect colorectal cancer (CRC) and
`advanced adenomas (AA). Cologuard is 92% sensitive for detection of CRC. Cologuard is a statistically
`superior noninvasive stool test for detecting CRC and AA, as shown in a head-to-head, cross-sectional clinical
`study of Cologuard and a commercially available fecal immunochemical test (OC FIT-CHEK, Polymedco, Inc.)
`(“FIT”). In the study, Cologuard specificity was 87% (the specificity calculation excluded both CRC and AA),
`which is lower than that of FIT.
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`Cologuard is designed to analyze patients’ stool for the presence of 11 molecular markers, including
`hemoglobin and DNA markers, which may indicate the presence of colorectal cancer or advanced adenomas.
`Because cellular exfoliation of DNA into stool occurs continuously, Cologuard can detect pre-malignant
`neoplasia at early onset of abnormality.
`
`Based on combined results of all of the DNA markers and hemoglobin, a single Cologuard result is determined.
`Cologuard results are qualitative, positive or negative. A patient with a positive result should be referred to a
`diagnostic colonoscopy. A patient with a negative result should continue with a regular screening schedule. If
`no result is obtained, a second stool collection may be requested.
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`Patient Samples for Cologuard
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`Patients are not required to undergo bowel preparation or follow dietary or medication restrictions in order to
`complete the test. Patients follow the detailed instructions in the Cologuard Patient Guide received with the
`collection kit, consisting of a container for collection of stool for DNA testing and a separate sampler for
`collection of stool for hemoglobin testing. Both of these stool samples are required to obtain a Cologuard
`result. Samples are sent to a qualified laboratory for processing and testing.
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`Cologuard Compliance Program
`
`Cologuard includes a compliance program to handle collection kit shipment to the patient’s home in addition to
`live representatives for patient support, patient reminders, and billing and reimbursement questions. The
`compliance program also provides compliance tracking for physicians to measure and improve patient
`compliance.
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`Colorectal Cancer Overview
`Colorectal cancer (CRC) is the second leading cause of death from cancers affecting both men and women in
`the United States. One in 17 Americans will suffer from CRC during their lifetime; the lifetime risk is 35% higher
`for men than for women.1 Early detection by screening has been shown to reduce CRC mortality.2,3,4 Current
`guidelines for CRC screening in the average-risk population recommend initiation of screening at age 50 (age
`45 for African Americans), as the incidence of both CRC and premalignant lesions increases sharply after this
`age.5
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`Detection of potentially pre-malignant lesions, also known as advanced adenomas (AA), is essential for CRC
`prevention. Advanced adenomas include any size adenomas with carcinomas in situ or high grade dysplasia
`(HGD), adenomas with villous growth patterns (>25%), or adenoma ≥1.0 cm in size.6,7,8,9 Serrated lesions
`(polyps and sessile serrated adenoma) are typically found in the proximal colon, occur more frequently in the
`elderly, are often flat and inconspicuous endoscopically, and may have a more aggressive natural history than
`classic colorectal adenomas.9
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`Device Description
`Cologuard utilizes a multi-target approach to detect DNA and hemoglobin markers associated with CRC, as
`well as pre-malignant colorectal neoplasia (i.e., AA). Three independent categories of biomarkers are targeted
`and provide an additive association with CRC and pre-malignant colorectal neoplasia
`
`The first category of biomarkers involves epigenetic DNA changes characterized by aberrant gene promoter
`region methylation. The specific methylated gene targets include N-Myc Downstream-Regulated Gene 4
`(NDRG4) and the Bone Morphogenetic Protein 3 (BMP3).10,11 NDRG4 and BMP3 have been shown to be
`hypermethylated in colorectal cancer.1,10 The Cologuard procedure incorporates bisulfite conversion of non-
`methylated cytosine residues to uracil in the DNA sequence to enable sensitive detection of hypermethylated
`NDRG4 and BMP3.
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`The second category targets specific DNA point mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene
`homolog (KRAS) gene, which encodes a small GTPase that is activated transiently as a response to
`extracellular stimuli or signals.12,13,14 KRAS mutations have been detected in up to 35% of colorectal cancers
`and the 7 mutations in Exon 2 detected by Cologuard account for 98% of KRAS mutations.16 KRAS mutations,
`along with NDRG4 and BMP3 methylation markers, have been shown to be detected in the stool of subjects
`with colorectal neoplasia, including subjects with colorectal cancer and pre-malignant lesions. 15,16
`
`The third category of biomarker is non-DNA based and detects hemoglobin, which can be associated with
`colonic bleeding. Results from the methylation, mutation, and hemoglobin assays are combined in the
`laboratory analysis to determine a positive or negative reportable result or no result.
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`Assay Technology
`
`The patient stool samples are processed at the laboratory to isolate the DNA for testing. Amplification and
`detection of methylated target DNA (NDRG4, BMP3), KRAS point mutations, and ACTB (a reference gene for
`quantitative estimation of the total amount of human DNA in each sample) is performed using the Quantitative
`Allele-specific Real-time Target and Signal Amplification (QuARTS™) technology. Multi-plexed QuARTS
`reactions are processed using a real-time cycler with each marker (NDRG4, BMP3, KRAS, and ACTB)
`monitored separately through independent fluorescent detection channels. The hemoglobin stool sample is
`prepared and analyzed in a quantitative Enzyme-Linked Immunosorbent Assay (ELISA) that determines the
`concentration of hemoglobin in the sample.
`
`Run control samples for both the QuARTS assays and hemoglobin assay are tested along with patient
`samples to show that the process has been performed appropriately. Results from the methylation, mutation,
`and hemoglobin assays are combined during analysis to determine a positive result, negative result, or no
`result.
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`Clinical Study: Multi-Target Colorectal Cancer Screening Test for the Detection of Colorectal
`Advanced Adenomatous Polyps and Cancer (DeeP-C)
`
`Overview
`
`Cologuard was the subject of a prospective, multi-centered, pivotal trial (“Multi-Target Colorectal Cancer
`Screening Test for the Detection of Colorectal Advanced Adenomatous Polyps and Cancer: DeeP-C Study”). A
`total of 12,776 patients were enrolled from 90 sites, including both colonoscopy centers and primary care sites.
`The results of the study demonstrated the safety and effectiveness of Cologuard as a screening test for the
`detection of markers associated with the presence of CRC and colorectal neoplasia. Cologuard demonstrated
`92.3% CRC sensitivity and 86.6% specificity (specificity in this study excludes CRC and AA), using
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`colonoscopy with histopathological confirmation as the reference method. These results met the protocol-
`specified criteria for primary performance measures and study success. The study results exceeded the
`prospectively specified sensitivity threshold by nearly 20%. The study further compared CRC and AA detection
`by Cologuard to a commercially available fecal immunochemical test (OC FIT-CHEK, Polymedco, Inc.) (“FIT”),
`successfully demonstrating superiority for CRC (p=0.0018) and AA (p<0.0001) sensitivity.
`Study Design
`
`The study was designed to enroll subjects of either sex between the ages of 50 and 84 years (inclusive), who
`were at average risk for development of colorectal cancer and asymptomatic for gastrointestinal symptoms
`warranting diagnostic colonoscopy. In addition, subject enrollment was age-weighted toward a slightly older
`population to increase the point prevalence of colorectal cancer in this study. 64% of subjects in the actual
`study population were of age 65-84.
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`Subjects participating in the pivotal trial provided a stool sample and subsequently underwent colonoscopy
`within 90 days of study enrollment. Subjects collected stool samples for Cologuard and FIT testing at home.
`Subjects then underwent colonoscopy per standard of care. Subjects and physicians remained blinded to the
`results of Cologuard and the FIT. Results from Cologuard and the FIT test were compared to the results of the
`colonoscopy examination and histopathologic diagnosis of all significant lesions either biopsied or removed.
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`Negative colonoscopy findings were categorized as negative (Table 1, category 6.2). Histopathological results
`from biopsied tissue or excised lesions were categorized based on the most clinically significant lesion present
`(i.e. the index lesion) by a central pathologist according to the pre-specified standards outlined in Table 1.
`Sensitivity analysis was performed using positive findings in categories 1 and 2 while specificity was calculated
`using categories 3 through 6 (all findings excluding CRC and AA).
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`
`Category
`1
`2
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`3
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`4
`5
`6
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`Table 1: Category definitions
`Findings
`CRC, all stages (I-IV)
`Advance adenoma, including the following subcategories:
`2.1 – Adenoma with carcinoma in situ/high grade dyplasia, any
`size
`2.2 – Adenoma, villous growth pattern (>25%), any size
`2.3 – Adenoma > 1.0 cm in size, or
`2.4 – Serrated lesion, > 1.0 cm in size
`1 or 2 adenoma (s), >5 mm in size, or < 10 mm size, non-
`advanced
`> 3 adenomas, <10mm, non-advanced
`1 or 2 adenoma(s), ≤5 mm in size, non-advanced
`Negative – No neoplastic findings
`6.1 – negative upon histopathological review
`6.2 – no findings on colonoscopy, no histopathological review
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`Study Population and Baseline Demographics
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`Study enrollment and population demographics are summarized in Figure 1. A total of 10,023 subjects with
`colonoscopy and Cologuard data were included in the primary analysis population. This population included 65
`subjects with CRC. Analysis was conducted to rule out bias associated with the subjects excluded from the
`analysis population.
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`The average age of subjects included in the primary analysis was 64.2 years, and there were a slightly higher
`percentage of female subjects (5,378/10,023, 53.7%) as compared with male subjects (4,645 /10,023, 46.3%).
`Two 49-year-old subjects and one 44-year old subject were included in the study, which is inconsistent with the
`intended user population. Each of these subjects was a true negative on Cologuard and their inclusion did not
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`notably impact data analyses. The majority of subjects were White (8,422/10,023, 84.1%), although 10.7% of
`the population were Black or African American subjects (1,071/10,023). Nearly 10% of subjects were Hispanic
`or Latino (991/10,023, 9.9%). Average BMI was 28.8 and the majority of subjects never smoked (5.531
`/10,023, 55.2%).
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`Figure 1: Clinical Study Demographics
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`Total Enrollment 12,776
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`Primary Endpoint
` Valid Cologuard + Colonoscopy
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` 10,023
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`Secondary Endpoint
` Valid Cologuard + FIT + Colonoscopy 9,989
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`Clinical Performance Measures
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`The primary and secondary performance measures for the clinical study are summarized in Table 2 below. The
`primary performance measures were the sensitivity and specificity of Cologuard for CRC, using colonoscopy
`with histopathology as the reference method. The primary analysis required that the lower bound of the 95%
`one-sided confidence interval for the sensitivity of Cologuard for CRC exceed 65%. The specificity analysis for
`CRC required that the lower bound of the one-sided 95% confidence interval exceed 85%.
`
`With respect to the secondary performance measure, Cologuard was compared to FIT using a non-inferiority
`test for CRC sensitivity and using a superiority test for advanced adenoma (AA) sensitivity. In order for
`Cologuard to be deemed non-inferior to FIT, the one-sided 95% confidence interval lower bound for the
`Cologuard – FIT difference in percentages with a positive test among subjects with CRC was required to
`exceed -5%. Establishing superiority required a one-sided p-value <0.025 (exact McNemar’s comparison test).
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`Table 2: Clinical Study Primary and Secondary Performance Measures
`Primary Performance
`
`(cid:120) Determine the CRC sensitivity and specificity of Cologuard.
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`measures
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`Secondary
`Performance
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`measures
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`(cid:120) Compare Cologuard to FIT for CRC and AA sensitivity.
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`Summary of Clinical Study Results
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`Results from the clinical study demonstrated that Cologuard successfully met the primary performance
`measure of the study, establishing a clinically meaningful sensitivity and specificity for CRC. Sensitivity of
`Cologuard for CRC was 92.3% (60/65) with a one-sided 95% confidence interval lower bound of 84.5,
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`substantially exceeding the protocol-specified threshold of 65%. In addition, Cologuard successfully
`demonstrated a clinically meaningful specificity according to the protocol-specified criteria. The specificity of
`Cologuard was 86.6%, with a one-sided 95% confidence interval lower bound of >86.0%.
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`Clinical study results demonstrated superiority of Cologuard to FIT for sensitivity in detecting CRC. Secondary
`performance measures included an analysis of performance Cologuard and FIT using colonoscopy as a
`reference. Cologuard correctly detected 60 of the 65 total CRC cases identified by colonoscopy (92.3%). FIT
`captured only 48 of the 65 CRC cases identified by colonoscopy (73.8%). FIT identified only a single cancer
`that was not identified by Cologuard. Cologuard, meanwhile, identified 13 cancers that were missed by FIT.
`Cologuard was compared to FIT using a non-inferiority test for CRC sensitivity. In addition, Cologuard
`demonstrated superiority over FIT with respect to sensitivity for CRC using an exact McNemar’s comparison
`test as the one-sided p-value (p=0.0018) was well below the p <0.025 threshold for superiority. The lower
`bound of the one-sided confidence interval for the Cologuard – FIT difference was 0.080, substantially
`exceeding the protocol-specified non-inferiority threshold of -0.05.
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`Establishing superiority for AA sensitivity required a one-sided p-value <0.025 (exact McNemar’s comparison
`test). Cologuard demonstrated superiority for AA sensitivity, with a p-value of <0.0001, substantially below the
`threshold for superiority of p<0.025. FIT identified only 29 AA cases that were not captured by Cologuard,
`while Cologuard identified 170 AA cases that were not positive on the FIT test.
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`Analysis was also performed to calculate the Cologuard negative predictive value (NPV) for Category 1 (CRC)
`and Category 2 (AA). Clinical results show that a negative patient result for Cologuard gives 99.94% assurance
`that the patient does not have cancer and a 94.79% chance that the patient does not have an advanced
`adenoma.
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`Cologuard and FIT Performance Comparison
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`Cologuard was superior to FIT for both CRC and AA detection. Cologuard also demonstrated high sensitivity
`for detection of lesions and polyps which historically have been difficult to capture with FIT, including early
`stage CRC, proximal lesions, and higher risk precancerous lesions. Cologuard demonstrated a numerically
`greater sensitivity than FIT for detection of CRC and AA across lesion subgroups. Sensitivity results are
`summarized in Table 3 and Table 4 below. As noted above, Cologuard specificity was 86.6% and FIT
`specificity was 95%. These specificity measures excluded CRC and AA for both tests.
`
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`Cologuard sensitivity for stage I cancer was 89.7% compared to 65.5% for FIT (p=0.039). Sensitivity for stage
`II cancer was 100.0% for Cologuard compared to 76.2% for FIT (p=0.062). CRC sensitivity was also compared
`to FIT by size of the lesion, with higher detection at each lesion size than FIT. When analyzed by lesion
`location, Cologuard showed 90.0% sensitivity for proximal cancer compared to 66.7% for FIT (p=0.039).
`Cologuard also detected higher risk precancerous lesions, including high grade dysplasia (69.2% Cologuard,
`46.2% FIT, p=0.004) and sessile serrated polyps (43.0% Cologuard, 5.1% FIT, p<0.001). Cologuard and FIT
`were both better at detecting precancerous lesions as lesion size increased from 0.5 cm to ≥3 cm (value for
`trend for both was p<0.001).
`
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`Table 3: Cologuard and FIT Cancer Sensitivity
`Cologuard
`Sensitivity
`
`n=
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`65
`29
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`92.3%
`89.7%
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`Subgroup
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`Cancer Stage
`CRC, all stages (p=0.018)
`Stage I (p=0.039)
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`FIT
`Sensitivity
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`73.8%
`65.5%
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`Stage II (p=0.062)
`Stage III
`Stage IV
`Stage I-III (p=0.002)
`Cancer Size
`< 5 mm
`5-9 mm
`10-19 mm
`20-29 mm
`≥30 mm
`Cancer location
`Proximal (p=0.039)
`66.7%
`90.0%
`30
`Distal (p=0.062)
`80.0%
`94.3%
`35
`*Cologuard specificity was 86.6% and FIT specificity was 95%. These specificity measures excluded CRC and AA
`for both tests.
`
`21
`10
`4
`60
`
`0
`5
`14
`12
`34
`
`100.0%
`90.0%
`75.0%
`93.3%
`
`0
`80.0%
`92.9%
`91.7%
`94.1%
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`76.2%
`90.0%
`75.0%
`73.3%
`
`0
`60.0%
`85.7%
`66.7%
`73.5%
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`Table 4: Cologuard and FIT Advanced Adenoma Sensitivity
`Cologuard
`Cologuard
`FIT
`n=
`Sensitivity
`n=
`
`Subgroup
`
`FIT
`Sensitivity
`
`760
`39
`100
`
`42.4%
`69.2%
`43.0%
`
`757
`39
`99
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`23.8%
`46.2%
`5.1%
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`Pre-malignant Neoplasia
`AA, all subcategories (p<0.001)
`High grade dysplasia (p-0.004)
`Sessile serrated ≥10 mm (p<0.001)
`AA location
`Proximal (p<0.001)
`15.5%
`431
`33.0%
`433
`Distal (p<0.001)
`34.8%
`325
`54.6%
`326
`Lesion Size
`p value for trend<0.001
`p value for trend<0.001
`< 5 mm
`10
`20.0%
`10
`20.0%
`5-9 mm
`56
`14.3%
`56
`32.1%
`10-19 mm
`574
`20.9%
`577
`39.0%
`20-29 mm
`79
`43.0%
`79
`64.6%
`≥30 mm
`38
`42.1%
`38
`68.4%
`*Cologuard specificity was 86.6% and FIT specificity was 95%. These specificity measures excluded CRC and AA
`for both tests.
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`
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`
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`Cologuard Subgroup Analysis: please note that the clinical study was not designed to evaluate subgroups
`and subgroup analysis should be interpreted with that in mind.
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`The clinical study results were analyzed according to various demographic characteristics, including gender,
`age, and race/ethnicity as summarized in Table 5 below. Although CRC sensitivity was higher for males versus
`females and higher in Whites and Asians compared to Black/African Americans, AA sensitivity and specificity
`remained consistent across subgroups, with only a few differences likely attributed to a lower number of
`subjects from all subpopulations in the study.
`
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`Cologuard CRC sensitivity was higher for males versus females. Meanwhile, specificity of Cologuard was
`similar for females as compared with males. Specificity was 87.3% (4,398/5,037) for females, compared with
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`85.8% (3,569/4,161) for male subjects. Advanced adenoma detection showed similar results between males
`and females.
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`For age, Cologuard sensitivity for CRC was consistently high across all age groups. Sensitivity for patients 65
`years of age and older ranged from 88.9% to 100.0%. Although sensitivity was 75% for subjects age 60-64, the
`number of CRC cases was particularly small in this age group (n = 4); only one CRC case was not detected by
`Cologuard. With respect to AA, sensitivity was similar across all age groups, with sensitivity as high as 46.8%
`for subjects between the ages of 70 and 79. Cologuard specificity for CRC was also high across all age
`groups. Specificity was in the 80% range or above for most age groups, aside from subjects > 75 years old.
`Specificity for AA was also similar across age groups.
`
`Cologuard CRC sensitivity was very high among White subjects, but lower among Black or African-American
`subjects) and high among the small number of Asian CRC cases. However, the results observed in
`Black/African-American subjects may have been affected by the low overall number of cancer cases in that
`subpopulation. Sensitivity among Hispanic or Latino subjects was high, although the sample size was small.
`
`Cologuard sensitivity for AA was similar for White and Black/African-American subjects. Sensitivity was also
`similar among Hispanic/Latino subjects. AA sensitivity was lower among Asian subjects and very high for
`American Indian or Alaskan Natives, compared with other groups. Only the American Indian and Alaskan
`Native subpopulations showed higher sensitivity in AA detection. Differences between racial and ethnic
`subpopulation results may be affected by the small number of subjects in the African American and American
`Indian or Alaska Native subpopulations. Cologuard specificity was high across all racial and ethnic groups, with
`rates > 85% for most groups.
`
`Table 5: Cologuard Performance by Subgroup
`CRC Sensitivity
`AA sensitivity
`
`Subgroup
`
`Specificity
`
`Gender
`Male
`Female
`Age
`<60 yrs
`60-64 yrs
`65-69 yrs
`70-74 yrs
`75-79 yrs
`>79 yrs
`Race
`White
`Black or African American
`Asian
`American Indian or Alaska Native
`Native Hawaiian or Other Pacific
`Islander
`Other
`Ethnicity
`Hispanic or Latino
`Not Hispanic or Latino
`
`34/34 (100%)
`26/31 (83.9%)
`
`201/450 (44.7%)
`121/310 (39%)
`
`3569/4161 (85.8%)
`4398/5037 (87.3%)
`
`7/7 (100.0%)
`3/4 (75.0%)
`19/20 (95.0%)
`16/18 (88.9%)
`6/6 (100.0%)
`9/10 (90.0%)
`
`53/55 (96.4%)
`5/8 (62.5%)
`1/1 (100.0%)
`0/0
`0/0
`1/1 (100.0%)
`
`65/171 (38.0%)
`24/57 (42.1%)
`125/301 (41.5%)
`72/154 (46.8%)
`29/62 (46.8%)
`7/15 (46.7%)
`
`271/641 (42.3%)
`36/85 (42.4%)
`4/13 (30.8%)
`3/4 (75.0%)
`0/0
`7/16 (43.8%)
`
`2491/2703 (92.2%)
`681/765 (89.0%)
`2871/3352 (85.7%)
`1292/1566 (82.5%)
`480/617 (77.8%)
`152/195 (77.9%)
`
`6639/7726 (85.9%)
`879/978 (89.9%)
`229/245 (93.5%)
`24/32 (75.0%)
`21/23 (91.3%)
`171/189 (90.5%)
`
`8/9 (88.9%)
`52/56 (92.9%)
`
`23/59 (39.0%)
`298/700 (42.6%)
`
`837/923 (90.7%)
`7127/8272 (86.2%)
`
`
`441 Charmany Dr
`Madison WI, 53719
`844-870-8870
`RX Only
`
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`Geneoscopy Exhibit 1080, Page 9
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`

`Ordering Cologuard
`Cologuard is available for physicians to order through the Exact Sciences Laboratories online portal at
`www.CologuardTest.com or through paper requisition. Cologuard includes a compliance program and provides
`attentive service to physicians and patients with live operators. For any questions about Cologuard or specific
`questions on how to order the test, please contact Exact Sciences Laboratories.
`
`Exact Sciences Laboratories
`145 E. Badger Rd, Suite 100
`Madison, WI 53713
`844-870-8870
`
`Sample Colle